BackgroundThe use of Complementary and Alternative Medicine (CAM) has been increasing over the years. A recent review of adverse event reports (AERs) associated with CAM in Singapore found a notable number of AERs submitted. The objectives of this study are to analyse hepatotoxicity cases associated with CAM in Singapore based on spontaneous adverse event reporting to the Health Sciences Authority (HSA), and to highlight safety signals for specific herbal ingredients.MethodsAERs associated with CAM and hepatotoxicity submitted to the Vigilance and Compliance Branch (VCB) of the HSA from 2009 to 2014 were compiled. The following information was extracted and analysed: Demographic information; time to onset; hospitalisation status; outcome; type of hepatotoxicity; ingredients of CAM, and the total daily doses (TDD); concurrent western medicines and health supplements; and reporter details.ResultsFifty-seven reports were eligible for analysis. Thirty-five (61.4 %) cases involved Traditional Chinese Medicine (TCM). The Roussel Uclaf Causality Assessment Method was applied in 29 (82.9 %) of these cases, and the median score was 4 (range: 1–8). Chai Hu (Radix bupleuri) was suspected in 11 (31.4 %) cases. TDDs of most ingredients were within recommended doses of the Chinese Pharmacopoeia.ConclusionsDrug-induced liver injury is still poorly understood and more objective assessments are warranted. Reporting of adverse events should be strongly advocated to facilitate future analyses and the understanding of risk-benefit profiles of CAM.

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Syndecan-2 and FGF-2 are not only overexpressed in keloid tissues but may interact with each other resulting in the shedding of syndecan-2, which in turn might activate a whole cascade of events responsible for a keloidic phenotype. In addition, decorin had an antifibrotic effect and could well be used as a potential therapeutic agent for keloids.

We analyzed the spontaneous adverse event database in Singapore to determine the types of cutaneous adverse drug reactions ( CADR s) and causative drugs reported. We selected 10 CADR s‐of‐interest, and identified the suspected drugs and the characteristics of the at‐risk population. ADR reports received from 2006 to 2015 of the system organ class “Skin and Appendages Disorders” were analyzed based on patient demographics, the types of CADR s, suspected drugs, outcome, and latency period. Of the 104 372 reports analyzed, 56.2% involved females and 72.5% involved Chinese patients. The mean age was 41.1 years old. The top CADR s reported were rash (including nonspecified rash, follicular rash, maculopapular rash, and vesicular rash) (67.2%) and angioedema (13.9%). The drugs frequently associated with the CADR s‐of‐interest include nonsteroidal antiinflammatory drugs and antibiotics with angioedema, iohexol with urticaria, and antiepileptics and allopurinol with Stevens‐Johnson syndrome ( SJS )/toxic epidermal necrolysis ( TEN ). A subgroup analysis based on age, sex, and race on the 10 CADR s‐of‐interest showed the following trends in reporting: Alopecia (reported more in females), drug hypersensitivity syndrome (more in males), angioedema (more in younger patients), and photosensitivity (more in older patients). In general, the racial distribution across each CADR ‐of‐interest was consistent with that of Singapore's population, with slight deviations observed for SJS / TEN , photosensitivity and skin discoloration. We analyzed CADR reports from Singapore over 10 years, and identified the types of CADR s reported, and their associated drugs, latency periods and patient characteristics. Such information could add value to healthcare professionals as they assess CADR cases and evaluate suspected drugs.

Keloid scars are fibroproliferative disorders characterized by the accumulation of extracellular matrix (ECM) components resulting in a fibrotic condition. Several ECM promoters are regulated by Sp1. Thus, our aim was to investigate the role of Sp1 in keloid pathogenesis and investigate the antiproliferative and antifibrotic effects of Wp631 and mitoxantrone, potent inhibitors of Sp1-activated transcription. An elevated level of Sp1 was observed in tissue extracts obtained from keloid tissue. Serum stimulation elevated Sp1 levels in keloid fibroblasts (KF). Under coculture conditions Sp1 seemed to be downregulated. Wp631 and mitoxanthrone in serum growth factors resulted in a reduced expression of ECM components in KF. Both Wp631 and mitoxanthrone were also able to inhibit the proliferation of normal and keloid keratinocytes and fibroblasts significantly. As Wp631 seems to be potent in downregulating the ECM components in KF and also inhibiting the proliferation of these cells it could be explored as a possible therapeutic agent in the treatment of keloids.

Objective: To investigate the effect of glucose and insulin concentrations on differentiation of umbilical cord lining progenitor cells to adipocyte-like cells (ALCs). Methods: Cord lining mesenchymal cells (CLMCs) were isolated from the explant of human umbilical cord amniotic membrane. CLMCs were subjected to differentiation under various culture conditions for 20 days. Lipid droplets were confirmed with Oil Red O staining. Gene expressions of adipsin and peroxisome proliferator-activated receptor gamma (PPARg) were analyzed using reverse transcription-PCR. Leptin and adiponectin secretions were detected using enzyme-linked immunosorbent assay kit. Results: CLMCs became irregular, cuboidal-shaped cells that resemble adipocytes, and Oil Red O staining showed the presence of lipid droplets. The gene expressions of PPARg and adipsin were upregulated. Leptin and adiponectin secretions by naive CLMCs were below the limits of detection. Matured ALCs cultured in low-glucose medium significantly secreted leptin and adiponectin, whereas those in high-glucose medium significantly secreted only leptin. Insulin concentration affects leptin but not adiponectin secretion. Conclusions: Under different culture conditions, CLMCs can differentiate into ALCs that resemble adipocytes in either normalweight or obese individuals. Hence, these ALCs have the potential to be used as an in vitro model to study adipogenesis and obesity, and possibly as a drug discovery model for metabolic disorders.

The primary hepatocyte is the best benchmark for drug biotransformation studies. However, due to the severe shortage of primary hepatocytes, there is a need for alternative reliable cell source. This study aims to isolate multipotent epithelial cells from the umbilical cord, differentiate these cells into hepatocyte-like cells (HLCs), and investigate the potential of using the differentiated cells for in vitro drug metabolism model. Human umbilical cord lining epithelial cells (UCLECs) were subjected to hepatic induction over a period of 28 days. HepG2 and cryopreserved human hepatocytes were used as control. Immunohistological staining was carried out for α-fetoprotein (AFP), albumin, cytokeratin 18 (CK18), and 19 (CK19). Glycogen storage ability was assessed through periodic acid-Schiff stain. Reverse transcription polymerase chain reaction was performed to examine gene expression of hepatic nuclear factor 4α (HNF4α) and cytochrome P450 isozymes 1A2, 2C9, 2D6, and 3A4. Ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS) was utilized to analyze functional metabolic ability of the HLCs, where CYP3A4 was chosen as the study focus and testosterone as the drug substrate. After 28 days of induction, the fibroblastic phenotype of UCLECs changed to rotund polygonal shape resembling that of hepatocytes. Protein expression of AFP and CK19 was negative, while albumin and CK18 expression was upregulated. Gene expression of HNF4α, CYP1A2, CYP2D6, and CYP3A4 was observed but not for CYP2C9. After 4 h of incubation with testosterone, UPLC/MS/MS detected 2α-, 6β-, 15β-, and 16β-hydroxytestosterone. UCLECs are able to differentiate into HLCs that express liver-specific markers, and have functional metabolic capabilities.

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